Chapter 11 - Modeling and remodeling: The cellular machinery responsible for bone's material and structural strength during growth, aging, and drug therapy

Abstract

Bone modeling and remodeling assemble bone's structure during growth. Abnormalities in this cellular machinery appear around midlife and cause microstructural deterioration and bone fragility. For over 60years, the gain and loss of bone strength have been inferred by measuring bone mineral density (BMD). This is an insensitive surrogate of bone fragility caused by microstructural deterioration, because microstructural deterioration compromises strength disproportionate to the bone loss producing it and the modest deficits in BMD found in most patients with fragility fractures. Quantification of microstructure is now available, but whether these measurements improve the detection of individuals at risk for fracture and improve treatment efficacy is unknown. Antiresorptive agents slow remodeling and microstructural deterioration. Anabolic agents may reconstruct bone, but available therapy produces mainly remodeling-based bone formation, which is limited for a range of reasons. Whether modeling-based bone formation or combined therapy offers better anti-fracture efficacy is unknown.